Complementary Medicine a Costly Risk in Management of Chronic Knee Osteoarthritis? A Case Report

@#Knee osteoarthritis is the commonest cause of knee pain in the elderly. It is characterized by unresolved pain, limitation of motion and reduced quality of life. Total knee arthroplasty (TKA) is a safe and effective method in treating chronic knee osteoarthritis. We report a rare case of a seventy-seven-year-old Chinese female with multiple comorbidities and bilateral degenerative osteoarthritis who had sought services of traditional and complementary medicine (TCM) for pain relief. The patient experienced unresolved pain and superficial skin scars following the unregulated procedure. This paper aims to outline the importance of awareness among surgeons regarding the unregulated practice of TCM that may exacerbate chronic osteoarthritis, joint synovitis, influence the surgical approach for future procedures with the presence of scars and prosthetic joint infection risk.

Single-stage revision of MRSA orthopedic device-related infection in sheep with an antibiotic-loaded hydrogel.

Local antimicrobial therapy is an integral aspect of treating orthopedic device-related infection (ODRI), which is conventionally administered via polymethyl-methacrylate (PMMA) bone cement. PMMA, however, is limited by a suboptimal antibiotic release profile and a lack of biodegradability. In this study, we compare the efficacy of PMMA versus an antibiotic-loaded hydrogel in a single-stage revision for chronic methicillin-resistant Staphylococcus aureus (MRSA) ODRI in sheep. Antibiofilm activity of the antibiotic combination (gentamicin and vancomycin) was determined in vitro. Swiss alpine sheep underwent a single-stage revision of a tibial intramedullary nail with MRSA infection. Local gentamicin and vancomycin therapy was delivered via hydrogel or PMMA (n = 5 per group), in conjunction with systemic antibiotic therapy. In vivo observations included: local antibiotic tissue concentration, renal and liver function tests, and quantitative microbiology on tissues and hardware post-mortem. There was a nonsignificant reduction in biofilm with an increasing antibiotic concentration in vitro (p = 0.12), confirming the antibiotic tolerance of the MRSA biofilm. In the in vivo study, four out of five sheep from each treatment group were culture-negative. Antibiotic delivery via hydrogel resulted in 10-100 times greater local concentrations for the first 2-3 days compared with PMMA and were comparable thereafter. Systemic concentrations of gentamicin were minimal or undetectable in both groups, while renal and liver function tests were within normal limits. This study shows that a single-stage revision with hydrogel or PMMA is equally effective, although the hydrogel offers certain practical benefits over PMMA, which make it an attractive proposition for clinical use.

Ceftobiprole: a potential empirical post-operative monotherapy in prosthetic joint infections.

BACKGROUND: This study aimed to evaluate in vitro susceptibility to ceftobiprole of clinical strains identified from prosthetic joint infections (PJIs) compared to that of the associations currently recommended for post-operative empirical antibiotic therapy (PEAT) (vancomycin with either cefepime, third-generation cephalosporin or piperacillin-tazobactam). METHODS: We performed a 1-year retrospective study on all the surgical procedures performed in our hospital for PJI. Susceptibility profiles of all the strains cultured from surgical samples were reviewed to compare ceftobiprole to current used associations. RESULTS: During the study period (from January 2018 to December 2018), we identified 106 patients managed for PJI and a total of 216 surgical interventions. One hundred-fifty strains were identified from intraoperative samples, excluding redundant strains. Staphylococcus spp. represented 52.7% of all strains and Enterobacteriales 13.3%. Twenty-three patients had polymicrobial infection (22%). Among 149 surgical procedures with positive culture results, ceftobiprole covered the bacterial strains in 138 (92.6%) cases. In comparison, this percentage was 94.6% for vancomycin plus cefepime (p = 0.64), 92.6% for vancomycin plus a third-generation cephalosporin in 138 cases (p = 1) and 94.6% for vancomycin plus piperacillin-tazobactam) (p = 0.64). CONCLUSION: Based on antimicrobial susceptibility testing, our results suggest that ceftobiprole could be an interesting option for PEAT in PJIs, allowing the use of a single agent.

Hospital Volume and Postoperative Infections in Total Knee Arthroplasty.

BACKGROUND: The purpose of this study was to evaluate the associations of hospital volume with revision surgery for infection and superficial incisional infections. METHODS: A review of 12,541 primary total knee arthroplasties (TKAs) at a large integrated health system from 2014 to 2017 was conducted. Sixteen hospitals were classified as low-volume, medium-volume, or high-volume hospitals according to the mean number of TKAs/year (<250, 250-500, and >500, respectively). Thresholds were guided by percentiles and the literature on volume-outcome relationships. Medical records were reviewed for revision surgery for infection and superficial incisional infections during a mean 2-year review period. Multivariate analyses, adjusted for clinical and patient characteristics, were performed to evaluate the association between hospital volume and infection. RESULTS: The overall rate of revision surgery for infection was 0.7% (n = 82), and the overall rate of superficial incisional infection was 2.6% (n = 324). After accounting for potential confounders, hospital volume was not found to have a significant association with revision surgery for infection when comparing high-volume and low-volume hospitals (odds ratio, 1.615; 95% confidence interval, 0.761-3.427; P = .212) as well as when comparing high-volume and medium-volume hospitals (odds ratio, 1.464; 95% confidence interval, 0.853-2.512; P = .166). Moreover, the risk of superficial incisional infection at high-volume hospitals was similar to that at low-volume (P = .107) and medium-volume (P = .491) hospitals. CONCLUSION: Infection outcomes are quality metrics that are frequently used to compare hospitals including those of varying volumes. Using contemporary thresholds, this study found that infection rates after TKA at high-volume hospitals are comparable to low-volume and medium-volume hospitals.

Antimicrobial characteristics of Berberine against prosthetic joint infection-related Staphylococcus aureus of different multi-locus sequence types.

BACKGROUND: Staphylococcal aureus (S. aureus) has become the leading causative pathogen of Prosthetic Joint Infection (PJI), which is the most devastating complication after arthroplasty surgeries. Due to the biofilm formation ability and emergence of multiple-drugs resistance strains of S. aureus, it has become an urgency to find new anti-staphylococcal agents to establish effective prophylaxis and treatment strategy for PJI. Extracted from a traditional Chinese herb, berberine is proved active in inhibiting S. aureus, while whether it exerts the same effect on PJI-related S. aureus remains unknown. This study aims to investigate the antimicrobial activity of berbrine against clinical derived PJI-related S. aureus and whether its inhibiting efficacy is associated with subtypes of S. aureus. METHODS: Eighteen PJI-associated S. aureus were collected and their Multi-locus Sequence Types (MLST) and susceptibility to berberine both in planktonic and biofilm form were investigated. Additionally, one S. aureus strain (ST1792) was selected from the group and its transcriptomic profiling in berberine incubation was performed. The statistical analyses were conducted using Student's t-test with SPSS 24.0(SPSS, IBM, USA). The data were expressed as the means ± standard deviation. Values of p < 0.05 were considered statistically significant. RESULTS: It was found out that the Minimum Inhibitory Concentration values of PJI-related S. aureus varied in a broad range (from 64 to 512 µg/ml) among different MLST subtypes and the bacteria were able to regain growth after 24 h in berberine of MIC value or higher concentrations. In addition, sub-inhibitory concentrations of berberine surprisingly enhanced biofilm formation in some S. aureus strains. CONCLUSION: Traditional medicine is utilised by a large number of individuals, which provides abundant resources for modern medical science. In our study, berberine was found bactericidal against PJI related S. aureus, however, its antibacterial property was impacted by the MLST subtypes of the bacteria, both in planktonic and biofilm growth forms.

Clinical Use of Colistin in Biofilm-Associated Infections.

Biofilm is an adaptive bacterial strategy whereby microorganisms become encased in a complex glycoproteic matrix. The low concentration of oxygen and nutrients in this environment leads to heterogeneous phenotypic changes in the bacteria, with antimicrobial tolerance being of paramount importance. As with other antibiotics, the activity of colistin is impaired by biofilm-embedded bacteria. Therefore, the recommendation for administering high doses in combination with a second drug, indicated for planktonic infections, remains valid in this setting. Notably, colistin has activity against metabolically inactive biofilm-embedded cells located in the inner layers of the biofilm structure. This is opposite and complementary to the activity of other antimicrobials that are able to kill metabolically active cells in the outer layers of the biofilm. Several experimental models have shown a higher activity of colistin when used in combination with other agents, and have reported that this can avoid the emergence of colistin-resistant subpopulations. Most experience of colistin in biofilm-associated infections comes from patients with cystic fibrosis, where the use of nebulized colistin allows high concentrations to reach the site of the infection. However, limited clinical experience is available in other scenarios, such as osteoarticular infections or device-related central nervous system infections caused by multi-drug resistant microorganisms. In the latter scenario, the use of intraventricular or intrathecal colistin also permits high local concentrations and good clinical results. Overall, the efficacy of intravenous colistin seems to be poor, but its association with a second antimicrobial significantly increases the response rate. Given its activity against inner bioflm-embedded cells, its possible role in combination with other antibiotics, beyond last-line therapy situations, should be further explored.

Colistin-containing cement spacer for treatment of experimental carbapenemase-producing Klebsiella pneumoniae prosthetic joint infection.

Carbapenemase-producing Enterobacteriaceae (CPE) are emerging multidrug-resistant bacteria responsible for invasive infections, including prosthetic joint infections (PJIs). Local administration of colistin may provide bactericidal concentrations in situ. This study evaluated the efficacy of a colistin-impregnated cement spacer, alone and in combination with systemic antibiotics, in a rabbit model of CPE-PJI. Elution of 3 MIU of colistimethate sodium (CMS) in 40 g of poly(methyl methacrylate) cement was studied in vitro. In vivo, 5 × 108 CFU of KPC-producing Klebsiella pneumoniae (colistin and meropenem MICs of 1 mg/L and 4 mg/L, respectively) were injected close to a prosthetic knee. Surgical debridement and prosthesis removal were performed 7 days later, and rabbits were assigned to six treatment groups (11-13 rabbits each): drug-free spacer; colistin-loaded spacer; colistin intramuscular (i.m.); colistin i.m. + colistin spacer; colistin i.m. + meropenem subcutaneous (s.c.); and colistin i.m. + meropenem s.c. + colistin spacer. Systemic treatment was administered at doses targeting pharmacokinetics in humans, and rabbits were euthanised 7 days later to evaluate bacterial counts in infected bones. In vitro, CMS elution was low (<0.1% at 24 h) but reached a local concentration of ≥20 mg/L (>20 × MIC). In vivo, combinations of local and systemic colistin, with or without meropenem, were the only regimens superior to the control group (P ≤ 0.05) in terms of viable bacterial counts and the proportion of rabbits with sterile bone, with no emergence of colistin-resistant strains. Colistin-loaded cement spacer in combination with systemic antibiotics were the most effective regimens in this CPE-PJI model.

Probabilistic chemotherapy in knee and hip replacement infection: the place of linezolid.

Prosthetic joint infection (PJI) can occur with a wide range of microorganisms and clinical features. After replacement surgery of prosthetic joint, prescription of probabilistic broad-spectrum antimicrobial therapy is usual, while awaiting microbial culture results. The aim of our study was to describe the antibiotic susceptibility of microorganisms isolated from hip and knee PJI. The data were collected to determine the best alternative to the usual combination of piperacillin-tazobactam (TZP) or cefotaxime (CTX) and vancomycin (VAN). Based on a French prospective, multicenter study, we analyzed microbiological susceptibility to antibiotics of 183 strains isolated from patients with confirmed hip or knee PJI. In vitro susceptibility was evaluated: TZP+VAN, TZP+linezolid (LZD), CTX+VAN, and CTX+LZD. We also analyzed resistance to different antibiotics commonly used as oral alternatives. Among the 183 patients with PJI, 62 (34%) had a total knee prosthesis, and 121 (66%) a hip prosthesis. The main identified bacteria were Staphylococcus aureus (32.2% of isolates), coagulase-negative staphylococci (27.3%), Enterobacteriaceae (14.2%), and Streptococcus (13.7%). Infections were polymicrobial for 28 (15.3%) patients. All combinations were highly effective: CTX+VAN, CTX+LZD, TZP+VAN, and TZP+LZD (93.4%, 94%, 98.4%, and 98.9% of all cases respectively). Use of LZD instead of VAN in combination with a broad-spectrum beta-lactam covers almost all of the bacteria isolated in PJI. This association should be considered in probabilistic chemotherapy, as it is particularly easy to use (oral administration and no vancomycin monitoring).

Addition of ceftaroline fosamil or vancomycin to PMMA: An in vitro comparison of biomechanical properties and anti-MRSA efficacy.

BACKGROUND: Ceftaroline is a cephalosporin that is effective against methicillin-resistant Staphylococcus aureus (MRSA) infections. The objective of this study was to determine the feasibility of using ceftaroline-loaded Polymethyl methacrylate (PMMA) as antibiotic cement against MRSA versus vancomycin-loaded PMMA in an in vitro setting. METHODS: PMMA pellets were prepared with three separate concentrations of each of the two antibiotics tested. They were tested to determine the effect of increasing concentration of antibiotics on the biomechanical properties of PMMA and antibiotic activity by measuring the zone of inhibition and broth elution assay. RESULTS: Ceftaroline PMMA at 3 wt%, three-point bending was 37.17 ± 0.51 N ( p < 0.001) and axial loading was 41.95 N ± 0.51 ( p < 0.001). At 5-wt% vancomycin-PMMA, three-point bending was 41.65 ± 0.79 N ( p = 0.02) and axial loading was 49.49 ± 2.21 N ( p = 0.01). Stiffness of ceftroline-loaded PMMA in low and medium concentration was significantly higher than the vancomycin. The zone of inhibition for ceftaroline was higher than vancomycin. Ceftaroline at 3 wt% eluted up to 6 weeks (0.3 ± 0.1 µg/ml) above the minimum inhibitory concentration (MIC) and vancomycin at 2.5 wt% eluted up to 3 weeks, same as MIC, that is, 0.5 ± 0.0 µg/ml. CONCLUSIONS: Ceftaroline, loaded at similar concentrations as vancomycin into PMMA, is a more potent alternative based on its more favourable bioactivity and elution properties, while having a lesser effect on the mechanical properties of the cement. The use of 3-wt% ceftaroline as antibiotic laden PMMA against MRSA is recommended. It should be noted that this was an in vitro study and to determine the clinical efficacy would need prospective, controlled and randomized studies.

Clonal diversity of Cutibacterium acnes (formerly Propionibacterium acnes) in prosthetic joint infections.

Prosthetic joint infections (PJIs) are rare but feared complications following joint replacement surgery. Cutibacterium acnes is a skin commensal that is best known for its role in acne vulgaris but can also cause invasive infections such as PJIs. Some phylotypes might be associated with specific diseases, and recently, a plasmid was detected that might harbour important virulence genes. In this study, we characterized C. acnes isolates from 63 patients with PJIs (n = 140 isolates) and from the skin of 56 healthy individuals (n = 56 isolates), using molecular methods to determine the phylotype and investigate the presence of the plasmid. Single-locus sequence typing and a polymerase chain reaction designed to detect the plasmid were performed on all 196 isolates. No statistically significant differences in sequence types were seen between the two study groups indicating that the C. acnes that causes PJIs originates from the patients own normal skin microbiota. Of the 27 patients with multiple tissue samples, 19 displayed the same sequence types among all their samples. Single-locus sequence typing identified different genotypes among consecutive C. acnes isolates from four patients with recurrent infections. The plasmid was found among 17 isolates distributed in both groups, indicating that it might not be a marker for virulence regarding PJIs. Patients presenting multiple sequence types in tissue samples may represent contamination or a true polyclonal infection due to C. acnes.

Activity of fixed direct electrical current in experimental Staphylococcus aureus foreign-body osteomyelitis.

Fixed DC was compared to ceftriaxone, ceftriaxone with 200 µA fixed DC, or no treatment in a rat model of methicillin-susceptible Staphylococcus aureus foreign-body osteomyelitis. After 3 weeks, fewer bacteria were present in bones of the ceftriaxone group (5.71 log10cfu/g [P = 0.0004]) and the ceftriaxone/DC group (3.53 log10cfu/g [P = 0.0002]) than untreated controls (6.70 log10cfu/g). Fewer bacteria were present in the ceftriaxone/DC group than in the ceftriaxone-alone and DC-alone groups (P = 0.0012 and 0.0008, respectively). There were also fewer bacteria on the implanted wires in the groups treated with ceftriaxone (5.47 log10cfu/cm2) or ceftriaxone/DC (2.82 log10cfu/cm2) than in the untreated controls (6.44 log10cfu/cm2 [P = 0.0003 and 0.0002, respectively]). There were fewer bacteria in the ceftriaxone/DC rats than in the ceftriaxone-alone- and fixed DC-alone-treated rats (P = 0.0017 and 0.0016, respectively). Fixed DC with an antibiotic may be useful for treating foreign-body infections caused by S. aureus.

A New Antibiotic-Loaded Sol-Gel Can Prevent Bacterial Prosthetic Joint Infection: From in vitro Studies to an in vivo Model.

The aim of this study was to evaluate the effect of a moxifloxacin-loaded organic-inorganic sol-gel with different antibiotic concentration in the in vitro biofilm development and treatment against Staphylococcus aureus, S. epidermidis, and Escherichia coli, cytotoxicity and cell proliferation of MC3T3-E1 osteoblasts; and its efficacy in preventing the prosthetic joint infection (PJI) caused by clinical strains of S. aureus and E. coli using an in vivo murine model. Three bacterial strains, S. epidermidis ATCC 35984, S. aureus 15981, and, E. coli ATCC 25922, were used for microbiological studies. Biofilm formation was induced using tryptic-soy supplemented with glucose for 24 h, and then, adhered and planktonic bacteria were estimated using drop plate method and absorbance, respectively. A 24-h-mature biofilm of each species growth in a 96-well plate was treated for 24 h using a MBECTM biofilm Incubator lid with pegs coated with the different types of sol-gel, after incubation, biofilm viability was estimated using alamrBlue. MC3T3-E1 cellular cytotoxicity and proliferation were evaluated using CytoTox 96 Non-Radioactive Cytotoxicity Assay and alamarBlue, respectively. The microbiological studies showed that sol-gel coatings inhibited the biofilm development and treated to a mature biofilm of three evaluated bacterial species. The cell studies showed that the sol-gel both with and without moxifloxacin were non-cytotoxic and that cell proliferation was inversely proportional to the antibiotic concentration containing by sol-gel. In the in vivo study, mice weight increased over time, except in the E. coli-infected group without coating. The most frequent symptoms associated with infection were limping and piloerection; these symptoms were more frequent in infected groups with non-coated implants than infected groups with coated implants. The response of moxifloxacin-loaded sol-gel to infection was either total or completely absent. No differences in bone mineral density were observed between groups with coated and non-coated implants and macrophage presence lightly increased in the bone grown directly in contact with the antibiotic-loaded sol-gel. In conclusion, moxifloxacin-loaded sol-gel coating is capable of preventing PJI caused by both Gram-positive and Gram-negative species.

Antibiotic Elution Characteristics and Pharmacokinetics of Gentamicin and Vancomycin from a Mineral Antibiotic Carrier: An in vivo Evaluation of 32 Clinical Cases.

Introduction: Locally implanted antibiotic-eluting carriers may be a valuable adjuvant to the management of prosthetic joint infections. Aim: to assess local and plasma antibiotic concentrations as well as cumulative antibiotic urine excretion associated with clinical use of a gentamicin - or vancomycin-loaded mineral composite antibiotic carrier. Methods: 32 patients (male/female=19/13, mean age=56; 21-82 years) were prospectively followed after implantation of gentamicin (n=11), vancomycin (n=15), or a combination (n=7), using an antibiotic carrier (CERAMENT™|G or CERAMENT™|V, mean amount 11 (3-20) mL) during resection arthroplasty of the hip/knee. We measured antibiotic concentrations in plasma (1h, 3h, 24h, 48h and 72h post-implantation), urine (24h, 48h and 72h post-implantation) and in drain (n=15). Results: We observed low antibiotic concentrations in plasma (Gentamicin: 0.33 mg/L (95%-CI: 0.25-0.44) and vancomycin: 1.33 mg/L (95%-CI: 1.02-1.66)) and high concentrations in drain (Gentamicin: mean 57.8 mg/L (95%-CI: 45.8-69.7) and vancomycin: mean 234.4 mg/L (95%-CI: 198.9-269.7)). Use of a drain was associated with a statistically significant reduction in vancomycin urine excretion (55.6% (95% CI: 36.45-74.92) to 28.71% (95% CI: 13.07-44.35), p=0.042). A similar trend was observed for gentamicin (34.17% (95% CI: 24.62-43.72) to 16.22% (95% CI: 0-33.86), p=0.078). Conclusions: CERAMENT™G/V was associated with safe plasma concentrations and high local concentrations above minimum inhibitory concentration. Installation of a surgical drain results in removal of a substantial amount of antibiotics and reduces antibiotic urine excretion.

Moxifloxacin plus rifampin as an alternative for levofloxacin plus rifampin in the treatment of a prosthetic joint infection with Staphylococcus aureus.

OBJECTIVES: The combination of a fluoroquinolone with rifampin is one of the cornerstones in the treatment of prosthetic joint infections (PJI) caused by staphylococci. Moxifloxacin is highly active against methicillin-susceptible Staphylococcus aureus (MSSA) and, therefore, is an attractive agent to use. However, several studies reported a lowering in serum moxifloxacin levels when combined with rifampin. The clinical relevance remains unclear. We determined the outcome of patients with early acute PJI caused by MSSA treated with either moxifloxacin/rifampin or levofloxacin/rifampin. METHODS: Medical files of patients treated with moxifloxacin/rifampin (University Medical Centre Groningen) or levofloxacin/rifampin (Hospital Clinic Barcelona) were retrospectively reviewed (2005-2015). Treatment failure was defined as the need for revision surgery and/or suppressive therapy, death by infection or a relapse of infection during follow-up. RESULTS: Differences in baseline characteristics between the two cohorts were observed, but prognostic parameters for failure, as defined by the KLIC-score (Kidney failure, Liver cirrhosis, Index surgery, C-reactive protein and Cemented prosthesis), were similar in the two groups (2.9 [1.5 SD] for the moxifloxacin group vs. 2.2 [1.2 SD] for the levofloxacin group [P = 0.16]). With a mean follow-up of 50 months (36 SD) in the moxifloxacin group, and 67 months (50 SD) in the levofloxacin group (P = 0.36), treatment was successful in 89% vs. 87.5%, respectively (P = 0.89). None of the failures in the moxifloxacin group were due to rifampin- or moxifloxacin-resistant S. aureus strains. CONCLUSION: Our data indicate that moxifloxacin combined with rifampin is as clinically effective as levofloxacin/rifampin for early acute PJI caused by MSSA.

Topical adjuvants incompletely remove adherent Staphylococcus aureus from implant materials.

Adjuvant treatments including Betadine, Dakin's solution (sodium hypochlorite), or hydrogen peroxide (H2 O2 ) have been attempted to eradicate prosthetic joint infection caused by biofilm or intracellular bacteria. The purpose of this study was to evaluate the in vitro abilities of chemical adjuvants to decrease Staphylococcus aureus (S. aureus) biofilm presence on orthopaedic implant grade materials, including titanium, stainless steel, and cobalt chrome. S. aureus biofilms were grown for 48 h and evaluated for baseline colony forming units/centimeter squared (CFU/cm2 ) and compared to treatments with Betadine, Dakin's solution, H2 O2 , or 1% chlorine dioxide (ClO2 ). Control discs (n = 18) across all metals had an average of 4.2 × 107 CFU/cm2 . All treatments had statistically significant reductions in CFU/cm2 when compared to respective control discs (p < 0.05). For all metals combined, the most efficacious treatments were Betadine and H2 O2 , with an average 98% and 97% CFU/cm2 reduction, respectively. There were no significant differences between reductions seen with Betadine and H2 O2 , but both groups had statistically greater reductions than Dakin's solution and ClO2 . There was no change in antibiotic resistance patterns after treatment. Analysis of S. aureus biofilms demonstrated a statistically significant reduction in biofilm after a five-minute treatment with the modalities, with an average two log reduction in CFU/cm2 . Statement of clinical significance: While statistically significant reductions in CFU/cm2 were accomplished with chemical adjuvant treatments, the overall concentration of bacteria never fell below 105 CFU/cm2 , leading to questionable clinical significance. Further techniques to eradicate biofilm should be investigated. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1599-1604, 2018.

Rifampin-Based Combination Therapy Is Active in Foreign-Body Osteomyelitis after Prior Rifampin Monotherapy.

Staphylococcal prosthetic joint infections (PJIs) are associated with biofilm formation, making them difficult to treat; if managed with debridement and implant retention, rifampin-based therapy is usually employed. Rifampin resistance potentially challenges PJI treatment. In investigating the effects of rifampin monotherapy on methicillin-resistant Staphylococcus aureus (MRSA) foreign-body osteomyelitis in rats, we previously demonstrated that rifampin resistance was selected but that it disappeared 14 days following rifampin monotherapy (1) and that rifampin resistance occurred less frequently following two rounds than following one round of rifampin monotherapy (2). Here, we compared rifampin monotherapy followed by rifampin-vancomycin combination therapy to rifampin-vancomycin combination therapy alone in experimental MRSA foreign-body osteomyelitis. Animals treated with rifampin monotherapy followed by rifampin-vancomycin combination therapy had decreased quantities of bacteria 14 days following treatment completion (P = 0.034) compared to those in animals treated with combination therapy alone. Additionally, some isolates recovered from animals treated with combination therapy alone, although still susceptible to rifampin, had higher MIC, minimum biofilm-inhibitory concentration (MBIC), and minimum biofilm-bactericidal concentration (MBBC) values than those of the inoculating strain. This suggests that rifampin may remain a feasible treatment option in foreign-body-associated orthopedic infections following the selection of rifampin resistance.

In vitro activity of dalbavancin against biofilms of staphylococci isolated from prosthetic joint infections.

The in vitro activity of dalbavancin was tested against biofilms of 171 staphylococci associated with prosthetic joint infection. Dalbavancin minimum biofilm bactericidal concentration (MBBC) values were: MBBC50 for Staphylococcus aureus and Staphylococcus epidermidis, 1µg/mL; MBBC90 for S. aureus, 2µg/mL; MBBC90 for S. epidermidis, 4µg/mL.

Prosthetic joint infection caused by Trueperella bernardiae.

Trueperella bernardiae is a Gram-positive coryneform bacilli which role as human pathogen is unknown because it has been usually considered a contaminant. Furthermore its identification by biochemical test was difficult. We describe a prosthetic joint infection in a women who years ago underwent a total knee replacement with superinfection and necrosis of the patellar tendon as major complications. In the sample of synovial fluid collected grew a gram-positive bacilli which was identified by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) as T. bernardiae. The patient was treated with ciprofloxacin and currently preserves the prosthesis without signs of infection.

In vitro activity of ceftaroline against staphylococci from prosthetic joint infection.

We tested the in vitro activity of ceftaroline by Etest against staphylococci recovered from patients with prosthetic joint infection, including 97 Staphylococcus aureus isolates (36%, oxacillin resistant) and 74 Staphylococcus epidermidis isolates (74%, oxacillin resistant). Ceftaroline inhibited all staphylococci at ≤0.5 µg/mL. The ceftaroline MIC(90/50) values for methicillin-susceptible S. aureus, methicillin-susceptible S. epidermidis, methicillin-resistant S. aureus, and methicillin-resistant S. epidermidis were 0.19/0.125, 0.094/0.047, 0.5/0.38, and 0.38/0.19 µg/mL, respectively. Based on these in vitro findings, ceftaroline should be further evaluated as a potential therapeutic option for the treatment of prosthetic joint infection caused by methicillin-susceptible and methicillin-resistant S. aureus and S. epidermidis.

Effects of polysaccharide intercellular adhesin (PIA) in an ex vivo model of whole blood killing and in prosthetic joint infection (PJI): A role for C5a.

BACKGROUND: A major complication of using medical devices is the development of biofilm-associated infection caused by Staphylococcus epidermidis where polysaccharide intercellular adhesin (PIA) is a major mechanism of biofilm accumulation. PIA affects innate and humoral immunity in isolated cells and animal models. Few studies have examined these effects in prosthetic joint infection (PJI). METHODS: This study used ex vivo whole blood modelling in controls together with matched-serum and staphylococcal isolates from patients with PJI. RESULTS: Whole blood killing of PIA positive S. epidermidis and its isogenic negative mutant was identical. Differences were unmasked in immunosuppressed whole blood pre-treated with dexamethasone where PIA positive bacteria showed a more resistant phenotype. PIA expression was identified in three unique patterns associated with bacteria and leukocytes, implicating a soluble form of PIA. Purified PIA reduced whole blood killing while increasing C5a levels. In clinically relevant staphylococcal isolates and serum samples from PJI patients; firstly complement C5a was increased 3-fold compared to controls; secondly, the C5a levels were significantly higher in serum from PJI patients whose isolates preferentially formed PIA-associated biofilms. CONCLUSIONS: These data demonstrate for the first time that the biological effects of PIA are mediated through C5a in patients with PJI.